Pelis Ryan M, Wright Stephen H
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Physiology, University of Arizona, Tucson, Arizona, USA.
Curr Top Membr. 2014;73:233-61. doi: 10.1016/B978-0-12-800223-0.00006-2.
Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family--all of which are members of the major facilitator superfamily (MFS) of transporters--represent a mechanistically diverse set of processes, including the organic anion transporters (OATs and URAT1) that physiologically operate as organic anion (OA) exchangers, the organic cation transporters (OCTs) that operate as electrogenic uniporters of organic cations (OCs), and the so-called "novel" organic cation transporters (OCTNs) that support Na-cotransport of selected zwitterions. Whereas the OCTNs display a high degree of substrate selectivity, the physiological hallmark of the OATs and OCTs is their multiselectivity--consistent with a principal role in renal and hepatic clearance of a wide array of both endogenous and xenobiotic compounds. SLC47 consists of members of the multidrug and toxin extruder (MATE) family, which are carriers that are obligatory exchangers and that physiologically support electroneutral H⁺ exchange. The MATEs also display a characteristic multiselectivity and are frequently paired with OCTs to mediate transepithelial OC secretion, with the OCTs typically supporting basolateral OC entry and the MATEs supporting apical OC efflux. The SLC44 family contains the choline transporter-like (CTL) transporters. Largely restricted to choline and a limited set of structural congeners, the CTLs appear to support the Na-independent, electrogenic uniport of choline, thereby providing choline for membrane biogenesis. The solution of X-ray crystal structures of representative prokaryotic MFS and MATE transporters has led to the development of homology models of mammalian OAT, OCT, and MATE transporters that, in turn, have supplemented studies of the molecular basis of the complex interactions of ligands with these multiselective proteins.
溶质载体家族SLC22、SLC44和SLC47中的转运蛋白介导多种结构各异的有机电解质的转运，即那些在生理pH值下通常带电荷（阳离子、阴离子或两性离子）的分子。SLC22家族中的转运蛋白——它们都是主要转运体超家族（MFS）的成员——代表了一组机制多样的过程，包括作为有机阴离子（OA）交换体在生理上发挥作用的有机阴离子转运蛋白（OATs和URAT1）、作为有机阳离子（OC）的电生性单向转运体发挥作用的有机阳离子转运蛋白（OCTs），以及支持特定两性离子钠共转运的所谓“新型”有机阳离子转运蛋白（OCTNs）。虽然OCTNs表现出高度的底物选择性，但OATs和OCTs在生理上的标志是它们的多选择性——这与它们在肾脏和肝脏清除多种内源性和外源性化合物中所起的主要作用相一致。SLC47由多药和毒素外排（MATE）家族的成员组成，这些载体是强制性交换体，在生理上支持电中性H⁺交换。MATEs也表现出典型的多选择性，并且经常与OCTs配对以介导跨上皮OC分泌，其中OCTs通常支持基底外侧OC进入，而MATEs支持顶端OC流出。SLC44家族包含胆碱转运体样（CTL）转运蛋白。CTLs主要限于胆碱和一组有限的结构类似物，似乎支持胆碱不依赖钠的电生性单向转运，从而为膜生物合成提供胆碱。代表性原核MFS和MATE转运蛋白的X射线晶体结构解析导致了哺乳动物OAT、OCT和MATE转运蛋白同源模型的建立；反过来这些模型又补充了对这些多选择性蛋白质与配体复杂相互作用分子基础研究的不足
